Boronic acids, trifluoroborate salts and the corresponding N-methylimidoacetate (MIDA) complexes are used as synthetic intermediates for the synthesis of complex molecules using the Suzuki-Miyaura palladium catalyzed cross-coupling reaction. This reaction is used extensively in biomedical and pharmaceutical research. While a large number of aryl, heteroaryl and vinylboronic compounds are readily available, only a few alkyl and fewer still functionalized alkylboronic derivatives are available,
There are few methods that can be used to directly prepare boronic derivatives via hydroboration. These methods either used the strongly Lewis acidic haloboranes. HBX2 or the very sluggish catecholborane or pinacolborane. In both cases, these reagents reduce many functional groups. In general, dialkylborane are somewhat less reaction towards reduction and more selective in hydroborations readily forming the mixed borane, R2BR′. However, are very few methods that allow a selective removal of the two alkyl groups. The best known example of this reaction is the elimination of the isopinocampheyl groups using an aldehyde such as benzaldehyde or acetaldehyde to yield alpha-pinene and the boronic ester. The limitation to using the diisopinocampheylborane, Ipc2BH is significant reduction of functional groups, cost of the alpha-pinene used to prepare Ipc2BH. Also, the elimination does not always result in the formation of the desired product.
The one group reductive alkylation reaction has been known since the early 1960's. One equivalent of trialkylborane, R3B, is reacted with one equivalent of p-benozoquinone in an aqueous THF solution resulting in the preferential transfer of the more substituted alkyl group for the alkylhydroquinonone (reduction) and formation of a borinic acid, R2BOH. Despite a number of papers no one reported more than a one group transfer.
What is needed is a general method to prepare functionalized primary alkyl trifluoroborates and the corresponding boronic acids or esters without protecting and &protecting the functional group. Such methods would expand the scope and types of compounds that can be prepared using Suzuki-Miyaura reaction. In addition, boronic acids have been demonstrated biological activities and are also used as intermediates in other important organic reactions; therefore the development of methods that avoid laborious protection and deprotection of functional groups in the preparation of boronic acids or esters would significantly aid the field of organic synthesis.